Brachytherapy is a form of radiation treatment in which a radiation source is placed into or adjacent to a malignant tumor. There are two general categories of brachytherapy: high dose rate (HDR); and low dose rate (LDR). HDR brachytherapy involves the placement of a radiation source with high activity adjacent to or into the malignant tumor for a limited period of time. LDR brachytherapy involves the placement of a low activity radiation source adjacent to or into the malignant tumor for an indefinite period of time.
The radiation sources used in LDR brachytherapy are radioactive isotopes. The most common isotopes used in LDR brachytherapy are .sup.103 Pd (Palladium), .sup.125 I (Iodine), .sup.198 Au (Gold), and .sup.192 Ir (Iridium). These isotopes are packaged in a cylindrical titanium housing and are commonly referred to as isotope seeds. The typical dimensions of the seeds are 0.5 mm in diameter and 0.5-1.0 cm in length. The isotopes used in LDR brachytherapy are chosen for their low energy and short half life. Low energy provides for limited penetration of the radiation so that the radiation effect is limited to the tumor without affecting adjacent normal tissue. A short half life is desirable so that the radiation dose can be delivered in a reasonably short time frame.
For .sup.103 Pd and .sup.125 I, the zone of therapeutic effect is limited to about a 1 cm diameter sphere about the seed, so typically, a three-dimensional array of seeds is used to treat a tumor. In LDR brachytherapy of prostate cancer, over 100 seeds are typically used. Because solid tumors, such as those found in prostate cancer, are perceived to be diffuse, the entire organ is targeted.
To place multiple seeds into a three dimensional array, seeds can be delivered by needles using a two dimensional grid pattern, and longitudinal spacing. The two dimensional grid is usually defined by a needle guide, called a template. The template consists of a matrix of holes that guide the longitudinal advancement of the needles to insure their proper two dimensional position in the tumor. Once the two dimensional array of needles is established in the tumor, the seeds are deposited along the longitudinal axis of each needle. The spacing of the seeds along the longitudinal axis of the needle is accomplished by using biocompatible spacers between the seeds. The spacers and seeds are alternately inserted into the needle prior to placement of the needle into the tumor. Once the needle is placed into the tumor, a mandrel is used to maintain the position of the line of seeds and spacers as the needle is withdrawn. This leaves a line of seeds in their proper longitudinal position. This process is then repeated at the other two dimensional grid coordinates forming the desired three dimensional array of seeds.
LDR brachytherapy is an effective modality for treating localized malignancies, however, it is not always successful in eradicating the malignancy. Some tumors are resistant to the effect of radiation, and sometimes the placement of seeds is not optimal, leaving spaces that are under treated. To enhance the effectiveness of brachytherapy, adjunctive treatments are often used. These adjunctive treatments include external beam radiation therapy, hyperthermia, systemic chemotherapy, systemic hormonal therapy, and immunotherapy.
Often there is a synergistic effect between brachytherapy and the adjunctive therapy. Brachytherapy can destroy the majority of the malignant cells and injured the remaining malignant cells. The adjunctive therapy can eradicate the remaining injured cells. Alternatively, the adjunctive therapy can make the malignant cells vulnerable to the radioactive isotope from the brachytherapy, for example, by holding the cells in the radiosensitive part of the cell cycle (e.g., G2M, late G2 or G2/S). Examples of radiosensitizing agents include butyrate, gemcitabine, 5-fluorouracil, catalase, paclitaxel, and misonidazole.